1 Stroke is the leading cause of serious, chronic disability in adults worldwide. Over 750,000 new strokes 2 occur in the United States each year accounting for over half of all acute neurological hospital admissions. 3 While two-thirds of persons who suffer a stroke regain ambulatory function, the resulting gait pattern is slow, 4 asymmetrical and metabolically inefficient. Walking dysfunction represents one of the greatest physical 5 limitations post-stroke and improved walking is among the most frequently articulated goals of 6 neurorehabilitation. To date, rehabilitation for walking dysfunction post-stroke has produced highly variable 7 outcomes revealing minimal genuine change in walking function including walking speed or walking pattern. 8 Our long term goal is to improve walking post-stroke. The objective of this application is to investigate the 9 physiologic integrity of neural pathways sub-serving lower extremity function, including walking. The 10 rationale for our proposal stems from our previous work, which has identified distinct patterns of response to 11 therapeutic intervention for hemiparetic walking dysfunction, 'responders' and 'non-responders'. Responders 12 are characterized by significant changes in overground walking speed, multiple changes in spatio-temporal 13 coordination and marked strength changes in distal joints. In contrast, Non-responders produced minimal 14 changes in overground walking speed, few, if any, changes in spatio-temporal coordination, and small 15 strength changes in proximal joints. While the presence of responders and non-responders in the post- 16 stroke population is not surprising, at study baseline responders and non-responders could not be 17 differentiated using clinical instruments of motor impairment, activity, or walking speed. Moreover, clinical 18 characteristics of chronicity and severity failed to predict these patterns of response. Taken together, 19 however, our findings suggest the presence of differences in the functional connectivity of descending tracts 20 subserving key lower extremity muscle groups. 21 Based on our preliminary findings, the goal of this small project is to develop an assessment scheme that 22 will enable differentiation between individuals with the capacity for locomotor recovery from those who lack 23 such capacity. We propose to elaborate our existing methodological infrastructure to enable correlation of 24 neurophysiological functioning in the lower extremity/locomotor regions with clinical and behavioral 25 measures of walking. We will use transcranial magnetic stimulation (TMS) to probe brain regions 26 representing the lower extremity and determine the relationships between: 1) cortical excitability, 2) 27 functioning of and 3) differentiation between cortical and spinal level circuits, and 4) walking function. 28 Keywords: stroke, locomotion, recovery, neurophysiology, rehabilitation, biomechanics 29 30